Structure of FcRY, an avian immunoglobulin receptor related to mammalian mannose receptors, and its complex with IgY

Fc receptors transport maternal antibodies across epithelial cell barriers to passively immunize newborns. FcRY, the functional counterpart of mammalian FcRn (a major histocompatibility complex homolog), transfers IgY across the avian yolk sac, and represents a new class of Fc receptor related to the mammalian mannose receptor family. FcRY and FcRn bind immunoglobulins at pH ≤6.5, but not pH ≥7, allowing receptor–ligand association inside intracellular vesicles and release at the pH of blood. We obtained structures of monomeric and dimeric FcRY and an FcRY–IgY complex and explored FcRY's pH-dependent binding mechanism using electron cryomicroscopy (cryoEM) and small-angle X-ray scattering. The cryoEM structure of FcRY at pH 6 revealed a compact double-ring “head,” in which the N-terminal cysteine-rich and fibronectin II domains were folded back to contact C-type lectin-like domains 1–6, and a “tail” comprising C-type lectin-like domains 7–8. Conformational changes at pH 8 created a more elongated structure that cannot bind IgY. CryoEM reconstruction of FcRY dimers at pH 6 and small-angle X-ray scattering analysis at both pH values confirmed both structures. The cryoEM structure of the FcRY–IgY revealed symmetric binding of two FcRY heads to the dimeric FcY, each head contacting the CH4 domain of one FcY chain. FcRY shares structural properties with mannose receptor family members, including a head and tail domain organization, multimerization that may regulate ligand binding, and pH-dependent conformational changes. Our results facilitate understanding of immune recognition by the structurally related mannose receptor family and comparison of diverse methods of Ig transport across evolution

The infective cycle of Cabbage leaf curl virus (CaLCuV) is affected by CRUMPLED LEAF (CRL) gene in Arabidopsis thaliana

<p>Abstract</p> <p>Background</p> <p>Geminiviruses are single-stranded DNA viruses that cause serious crop losses worldwide. Successful infection by these pathogens depends extensively on virus-host intermolecular interactions that allow them to express their gene products, to replicate their genomes and to move to adjacent cells and throughout the plant.</p> <p>Results</p> <p>To identify host genes that show an altered regulation in response to <it>Cabbage leaf curl virus </it>(CaLCuV) infection, a screening of transposant <it>Arabidopsis thaliana </it>lines was carried out. Several genes were identified to be virus responsive and one, <it>Crumpled leaf </it>(<it>CRL) </it>gene, was selected for further characterization. <it>CRL </it>was previously reported by Asano et al., (2004) to affect the morphogenesis of all plant organs and the division of plastids. We report here that <it>CRL </it>expression, during CaLCuV infection, shows a short but strong induction at an early stage (3-5 days post inoculation, dpi). To study the role of <it>CRL </it>in CaLCuV infection, <it>CRL </it>over-expressing and silenced transgenic plants were generated. We compared the replication, movement and infectivity of CaLCuV in transgenic and wild type plants.</p> <p>Conclusion</p> <p>Our results showed that CRL over-expressing plants showed an increased susceptibility to CaLCuV infection (as compared to wt plants) whereas <it>CRL</it>-silenced plants, on the contrary, presented a reduced susceptibility to viral infection. The possible role of <it>CRL </it>in the CaLCuV infection cycle is discussed.</p

Food web structure and microenvironment affect Chagas disease vector infection and abundance in a rural landscape

Vector-borne pathogen transmission is shaped by multiple abiotic and biotic factors. Understanding the relative importance of these factors on vector abundance and infection is important for developing vector-borne disease control strategies. The crown of the Attalea butyracea palm provides a natural arboreal mesocosm suitable for studying how food web relations and microclimate affect Chagas disease vectors of the genus Rhodnius, which feed on vertebrate blood and interact with many vertebrate and invertebrate species, vegetation, and detritus within the palm crown. We performed a cross-sectional, observational study of A. butyracea crowns using a community ecology network approach to evaluate abiotic and biotic conditions associated with Rhodnius pallescens abundance and infection with Trypanosoma cruzi, the Chagas disease etiologic agent. We collected 1098 R. pallescens from 105 A. butyracea crowns in rural landscapes of Panama. In a palm subset (N = 49), we recorded microclimate and habitat conditions and counted vertebrate and invertebrate species in order to characterize palm crown food webs. We used food web metrics, namely Generality (average number of prey per predator) and Vulnerability (average number of predators per prey) to evaluate associations between palm community trophic structure, vector predators, vector blood meal species composition, vector abundance, and vector T. cruzi infection. Field data analyzed with generalized linear models showed that vector abundance and infection in a given palm crown were influenced by a combination of geographic location, land-use type, palm crown animal community composition, and microhabitat conditions. Vector abundance was negatively associated with increased overall palm crown community diversity. However, vector abundance was positively associated with the invertebrate predator and mammal community. R. pallescens Vulnerability score, which measures predation pressure on the vector within the palm crown, was positively associated with vector abundance. Vector infection with T. cruzi was positively associated with mammal presence; vectors in palms with mammals were about 25 times more likely to be infected with T. cruzi compared with vectors in palms without mammals. Our findings suggest that a holistic study of food webs and environmental variables at the local scale can provide useful information for vector-borne disease management across a wide habitat range

Superintegrability and higher order polynomial algebras II

In an earlier article, we presented a method to obtain integrals of motion and polynomial algebras for a class of two-dimensional superintegrable systems from creation and annihilation operators. We discuss the general case and present its polynomial algebra. We will show how this polynomial algebra can be directly realized as a deformed oscillator algebra. This particular algebraic structure allows to find the unitary representations and the corresponding energy spectrum. We apply this construction to a family of caged anisotropic oscillators. The method can be used to generate new superintegrable systems with higher order integrals. We obtain new superintegrable systems involving the fourth Painleve transcendent and present their integrals of motion and polynomial algebras.Comment: 11 page

CHR11, a chromatin-remodeling factor essential for nuclear proliferation during female gametogenesis in Arabidopsis thaliana

Chromatin-remodeling factors regulate the establishment of transcriptional programs during plant development. Although 42 genes encoding members of the SWI2/SNF2 family have been identified in Arabidopsis thaliana, < 10 have been assigned a precise function on the basis of a mutant phenotype, and none have been shown to play a specific role during the gametophytic phase of the plant life cycle. A. thaliana chromatin-remodeling protein 11 (CHR11) encodes an imitation of switch (ISWI)-like chromatin-remodeling protein abundantly expressed during female gametogenesis and embryogenesis in Arabidopsis. To determine the function of CHR11 in wild-type plants, we introduced a hairpin construct leading to the production of double-stranded RNA, which specifically degraded the endogenous CHR11 mRNA by RNA interference (RNAi). Transcription of the RNAi-inducing hairpin RNA was driven by either a constitutive cauliflower mosaic virus 35S promoter (CaMV35S) acting at most stages of the sporophytic phase or a newly identified specific promoter acting at the onset of the female gametophytic phase (pFM1). All adult trans-formants that constitutively lacked sporophytic CHR11 activity showed reduced plant height and small cotyledonary embryos with limited cell expansion. In contrast, RNAi lines in which CHR11 was specifically silenced at the onset of female gametogenesis (megagametogenesis) had normal height and embryo size but had defective female gametophytes arrested before the completion of the mitotic haploid nuclear divisions. These results show that CHR11 is essential for haploid nuclear proliferation during megagametogenesis and cell expansion during the sporophytic phase, demonstrating the functional versatility of SW12/SNF2 chromatin-remodeling factors during both generations of the plant life cycle

INVESTIGATION OF NUMERICAL AND PHYSICAL MODELLING EFFECTS ON THE CFD SIMULATION OF THE UNSTEADY FLOW IN AN HPT STAGE

ABSTRACT In order to investigate the unsteady flow behaviour in an HPT stage and the effects on the CFD solution of some numerical and physical modelling assumptions usually undertaken by the engineering community, an ITP in-house unsteady CFD code called Mu 2 s

Results of an international drug testing service for cryptomarket users

Introduction: User surveys indicate that expectations of higher drug purity are a key reason for cryptomarket use. In 2014-2015, Spain's NGO Energy Control conducted a 1-year pilot project to provide a testing service to cryptomarket drug users using the Transnational European Drug Information (TEDI) guidelines. In this paper, we present content and purity data from the trial. Methods: 219 samples were analyzed by gas chromatography associated with mass spectrometry (GC/MS). Users were asked to report what substance they allegedly purchased. Results: 40 different advertised substances were reported, although 77.6% were common recreational drugs (cocaine, MDMA, amphetamines, LSD, ketamine, cannabis). In 200 samples (91.3%), the main result of analysis matched the advertised substance. Where the advertised compound was detected, purity levels (m. ±. SD) were: cocaine 71.6. ±. 19.4%; MDMA (crystal) 88.3. ±. 1.4%; MDMA (pills) 133.3. ±. 38.4. mg; Amphetamine (speed) 51.3. ±. 33.9%; LSD 123.6. ±. 40.5. µg; Cannabis resin THC: 16.5. ±. 7.5% CBD: 3.4. ±. 1.5%; Ketamine 71.3. ±. 38.4%. 39.8% of cocaine samples contained the adulterant levamisole (11.6. ±. 8%). No adulterants were found in MDMA and LSD samples. Discussion: The largest collection of test results from drug samples delivered from cryptomarkets are reported in this study. Most substances contained the advertised ingredient and most samples were of high purity. The representativeness of these results is unknown

LAF1, a MYB transcription activator for phytochrome A signaling

The photoreceptor phytochrome (phy) A has a well-defined role in regulating gene expression in response to specific light signals. Here, we describe a new Arabidopsis mutant, laf1 (long after far-red light 1) that has an elongated hypocotyl specifically under far-red light. Gene expression studies showed that laf1 has reduced responsiveness to continuous far-red light but retains wild-type responses to other light wavelengths. As far-red light is only perceived by phyA, our results suggest that LAF1 is specifically involved in phyA signal transduction. Further analyses revealed that laf1 is affected in a subset of phyA-dependent responses and the phenotype is more severe at low far-red fluence rates. LAF1 encodes a nuclear protein with strong homology with the R2R3-MYB family of DNA-binding proteins. Experiments using yeast cells identified a transactivation domain in the C-terminal portion of the protein. LAF1 is constitutively targeted to the nucleus by signals in its N-terminal portion, and the full-length protein accumulates in distinct nuclear speckles. This accumulation in speckles is abolished by a point mutation in a lysine residue (K258R), which might serve as a modification site by a small ubiquitin-like protein (SUMO)

Revisión de las fórmulas magistrales (medicamentos individualizados) de mayor interés en dermatología pediátrica

En dermatología pediátrica, la correcta elección de la dosis de principio activo, así como del excipiente, se vuelve fundamental para conseguir los resultados terapéuticos deseados, por lo que se deben tener en cuenta aspectos tan variados como las características de la lesión, las del paciente y las del medicamento seleccionado. En la población pediátrica se plantean dificultades añadidas, tales como la limitada variedad de especialidades comerciales que se ajusten a sus particularidades. Por ello, la formulación magistral o formulación de medicamentos individualizados supone una buena alternativa terapéutica que permite emplear principios activos en los rangos terapéuticos aceptados, vehiculizados en las formas farmacéuticas idóneas, asociar varios en un mismo medicamento e incluso adaptar el vehículo al estado de la lesión, así como a las necesidades intrínsecas del paciente. Las formulaciones recogidas en este artículo, se basan en una amplia experiencia clínica y permiten a los médicos prescriptores adaptar el tratamiento de forma personalizada. The administration of appropriate doses of active ingredients and excipients is crucial for achieving desired treatment outcomes in pediatric dermatology. A number of factors need to be considered, including the characteristics of the lesion, the patient, and the drug. An additional challenge in pediatric settings is the limited number of commercially available formulations suitable for use in children. Drug compounding, which is the preparation of medications tailored to the needs of individual patients, is a good alternative for pediatric populations for a number of reasons. Using a customized compound, the clinician can prescribe formulations that contain the optimal dose of the active ingredients within acceptable limits and the most suitable vehicle and formulation components. Compounding can also be used to combine several active ingredients in a single medication and even adapt the vehicle to the characteristics of the lesion and the needs of the patient. The pharmaceutical formulations described in this review are based on extensive clinical experience and can be customized to meet individual needs